Until recently, the targets of approved anti-cancer immunotherapeutic agents have been limited to protein molecules. The approval of Unituxin, a chimeric anti-GD2 antibody, ch14.18 for the treatment of high-risk neuroblastoma in 2015, marks the first new agent targeting a glycolipid molecule, thereby widening the net of potential pharmaceutical targets. This was largely based on the pioneer work of Dr. Yu and her leadership during the entire course of ch14.18 development, from preclinical studies all the way through the final randomized phase III clinical trial. Another promising glycan target is O-acetyl GD2, which is overexpressed in neuroblastoma, melanoma, small cell lung cancer, glioblastoma, as well as cancer stem cells in glioblastoma and breast cancer. The lack of it expression in peripheral nerve fibers is also an advantage over GD2 as a therapeutic target. A monoclonal anti-O-acetyl GD2 has shown significant anti-tumor effects in preclinical animal models. Another promising cancer associated glyan is Globo H ceramide, which is over expressed in a variety of epithelial cancers. Dr. Yu’s group provided the first evidence that 1) Globo H and its precursor, Gb5 (SSEA3) are present in breast cancer stem cells; 2) Globo H-ceramide (GHCer) acts as an immune checkpoint by suppressing T and B cell immune responses; 3) GHCer is incorporated into endothelial cells, enhancing angiogenesis. Clinically, Globo H+ breast cancer specimens contained Globo H+ tumor infiltrating lymphocytes, and higher vessel density than Globo-H- tumors. Mechanistic investigations linked its angiogenic effects to its binding to TRAX, thereby releasing PLCb1 from TRAX to trigger Ca2+ mobilization. Thus, GHCer plays triple roles in serving as a cancer antigen (including breast cancer stem cells), as an immune checkpoint and as an angiogenic factor, thereby propelling the multi-national randomized phase II clinical trial of Globo H-KLH vaccine in metastatic breast cancer. The results showed significant prolongation of progression free survival in those patients who generated anti-Globo H antibody responses. A global phase III trial is underway.